Isolated hypoisoleucinemia impairs whole body but not hepatic protein synthesis in humans.

It is not known whether an acute decrease in the plasma concentration of any essential amino acid, as occurs during insulin infusion, impairs protein synthesis. To test this hypothesis in humans, selective hypoisoleucinemia or hypothreoninemia was induced by insulin infusion while maintaining normal or elevated plasma concentrations of the other amino acids via their selective infusion. The effects on protein synthesis were assessed using leucine kinetics and fractional synthetic rates of the two hepatic proteins albumin and fibrinogen. Results were compared with those of a combined insulin and complete amino acid infusion. Hypoisoleucinemia increased leucine oxidation (P less than 0.03) and decreased nonoxidative leucine disposal (P less than 0.04) and net leucine balance (P less than 0.03), whereas hypothreoninemia had no effect on any of these parameters. Neither hypoisoleucinemia or hypothreoninemia altered albumin and fibrinogen fractional synthetic rates when compared with the control study. Because of the known relationships between intra- and extracellular amino acid concentrations, the hypoisoleucinemia was most likely associated with a decreased intracellular concentration of isoleucine; such would not be the case for hypothreoninemia. Thus acute limited availability of a single essential amino acid can adversely affect nonhepatic protein synthesis.